Pulmonary endothelial cells regulate arterial levels of vasoactive substances by processes of uptake, release, catabolism or activation. We have demonstrated that one of these non-respiratory lung functions, converting enzyme activity, is modulated by oxygen tension, when studied in intact animals or in cultured endothelial cells. In preliminary studies, we have also shown that hyperoxic exposure impairs converting enzyme activity, then increases the converting enzyme activity in the portion of cells surviving O2- injury. Serotonin uptake is also impaired in these injured cells. We propose to compare the biochemical function of cultured endothelial cells from the lungs of fetal animals with cells from adult animals, lung and great vessels. We will investigate the mechanism of O2 modulation of converting activity and the nature of the cell component which senses a change in PO2 using pharmacologic and physicochemical methods. Fetal and adult derived cells will be biochemically characterized after acute and chronic exposures to hypoxic and hyperoxic gases with respect to converting enzyme activity, O2 modulation of converting enzyme activity, serotonin uptake and the concentration of both the Cu-Zn and Mn-superoxide dismutases. Also cell growth, morphology and morphometry of cell surface area, cell volume and organelle content will be performed in hypoxia and hyperoxia-exposed lung endothelial cells.